3HEY
Cyclic residues in alpha/beta-peptide helix bundles: GCN4-pLI side chain sequence on an (alpha-alpha-beta) backbone with cyclic beta-residues at positions 1, 4, 10, 19 and 28
Summary for 3HEY
| Entry DOI | 10.2210/pdb3hey/pdb |
| Related | 3C3G 3C3H 3HET 3HEU 3HEV 3HEW 3HEX |
| Descriptor | alpha/beta-peptide based on the GCN4-pLI side chain sequence with an (alpha-alpha-beta) backbone and cyclic beta-residues at positions 1, 4, 10, 19 and 28, ACETATE ION (3 entities in total) |
| Functional Keywords | helix bundle, foldamer, alpha/beta-peptide, de novo protein |
| Total number of polymer chains | 1 |
| Total formula weight | 4115.94 |
| Authors | Horne, W.S.,Price, J.L.,Gellman, S.H. (deposition date: 2009-05-10, release date: 2010-04-21, Last modification date: 2024-07-10) |
| Primary citation | Price, J.L.,Horne, W.S.,Gellman, S.H. Structural consequences of beta-amino acid preorganization in a self-assembling alpha/beta-peptide: fundamental studies of foldameric helix bundles. J.Am.Chem.Soc., 132:12378-12387, 2010 Cited by PubMed Abstract: We report high-resolution crystal structures of six new alpha/beta-peptide foldamers that have a regular alpha-residue/alpha-residue/beta-residue (alphaalphabeta) backbone repeat pattern. All of these foldamers were crystallized from aqueous solution, and all display four-helix bundle quaternary structure in the crystalline state. These oligomers are based on the well-studied 33-residue alpha-peptide GCN4-pLI, which is an engineered derivative of the dimerization domain of GCN4, a yeast transcription factor. GCN4-pLI forms a stable tetramer in solution and crystallizes as a four-helix bundle (Harbury et al. Science 1993, 262, 1401-1407). Previously we described a foldamer (designated 1 here) that was generated from GCN4-pLI by replacing every third alpha-amino acid residue with the homologous beta(3)-amino acid residue; this alphaalphabeta oligomer retains the side chain sequence of the original alpha-peptide, but the backbone contains 11 additional CH(2) units, which are evenly distributed (Horne et al. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 9151-9156). Despite the expanded backbone, 1 was found to retain the ability to form a tetrameric quaternary structure in which the individual molecules adopt an alpha-helix-like conformation. Here we compare nine analogues of 1 that have the same alphaalphabeta backbone but in which one or more of the flexible beta(3)-amino acid residues is/are replaced with an analogous cyclic beta-residue. The motivation for beta(3)-->cyclic replacements is to enhance conformational stability; however, a crystal structure of the one previously reported example (designated 2 here) revealed a "stammer" distortion of the helix-bundle architecture relative to 1. The results reported here suggest that the stammer is a peculiarity of 2, because all six of the new alpha/beta-peptides display undistorted four-helix bundle quaternary structures. More broadly, our results indicate that beta(3)-->cyclic replacements are generally well-accommodated in helix-bundle quaternary structure, but that such replacements can be destabilizing in certain instances. PubMed: 20718422DOI: 10.1021/ja103543s PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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